Rat interleukin‐2‐activated natural killer (A‐NK) cell‐mediated lysis is determined by the presence of CD18 on A‐NK cells and the absence of major histocompatibility complex class I on target cells

The precise mechanism by which target cells are recognized and subsequently lysed by interleukin‐2‐activated natural killer (A‐NK) cells is poorly understood. In this study the role of major histocompatibility complex (MHC) class I and adhesion molecules in the recognition and lysis of tumor cells was investigated in a syngeneic Wag rat model. Preincubation of tumor cells with F(ab′)₂ fragments of anti‐MHC class I monoclonal antibody (mAb) OX18 strongly enhanced the A‐NK cell‐mediated lysis. Also normal syngeneic cells such as T cells and A‐NK cells became highly sensitive for lysis by A‐NK cells after preincubation with mAb OX18. Two other mAb against MHC class I had no effect on lysis of target cells. These data indicate that masking of MHC class I on syngeneic tumor and normal cells by mAb OX18 is sufficient for A‐NK cells to recognize target cells as non‐self, resulting in lysis. In addition, we found that the presence of mAb against the β2 (CD18)‐integrins blocked the lysis of all tumor cell lines by A‐NK cells in ⁵¹Cr‐release assays, also when target cells were preincubated with mAb OX18. Because of the absence of CD18 on most tumor cells we concluded that a CD18‐associated integrin on A‐NK cells is essential for lysis of target cells. These results show that in this syngeneic rat model CD18 on A‐NK cells together with MHC class I on tumor cells determine A‐NK cell‐mediated lysis. Furthermore, we hypothesize that the anti‐MHC class I OX18 recognizes an epitope on rat MHC class I which is, or is very close to, the restriction element determining A‐NK cell‐mediated lysis.